Multisystem Effects of Repeated Co-codamol Exposure in Male Wistar Rats: Haematological, Biochemical, Oxidative, Inflammatory, Histopathological and Molecular-docking Evidence

Abstract

Co-codamol combines paracetamol (acetaminophen) and codeine, but the multisystem effects of repeated exposure to the combined formulation remain insufficiently characterised. This study evaluated the effects of repeated oral co-codamol administration on haematological, hepatic, renal, oxidative, inflammatory and histopathological parameters in adult male Wistar rats and examined predicted interactions of selected constituents with analgesia-associated molecular targets. Twenty rats were randomly allocated to four groups (n = 5). Groups A, B and C received co-codamol at 100, 97 and 90 mg/kg body weight, respectively, while Group D received normal saline. Treatments were administered orally once daily for 28 consecutive days. Repeated co-codamol exposure was associated with alterations in erythrocyte, leucocyte, platelet and red-cell indices. Changes were also observed in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and alkaline phosphatase activities, together with serum creatinine and urea concentrations. Hepatic and renal malondialdehyde, reduced glutathione, superoxide dismutase and total protein were assessed, with treatment-associated alterations observed in several of these parameters. Hepatic and renal IL-6 and IL-10 concentrations were also altered. Histopathological examination demonstrated treatment-associated changes in liver and kidney tissues. Molecular docking showed favourable predicted interactions between codeine and selected analgesia-associated targets. The measured responses were not uniformly proportional to dose across all endpoints. Overall, repeated co-codamol exposure was associated with multisystem biological alterations under the experimental conditions, while the docking findings provide computational hypotheses that require experimental validation.